Heme/onc Flashcards
What organs are responsible for hematopoiesis in utero?
What is the time frame?
What hemoglobin chains does each make?
Yolk sac: primary organ weeks 3 - 6. Makes embryologic forms of Hb using the chains: alpha, epsilon, gamma, zeta
Liver: primary organ week 6-22. Makes ONLY fetal Hb so only makes alpha and gamma chains.
Bone marrow: primary organ week 22 to birth. Makes only adult forms of Hb (A and A2) so only makes alpha, beta, delta chains
Why shouldn’t you test for G6PD during an acute crisis?
Because you should have higher amounts of immature RBCs (reticulocytes) and these cells will have higher G6PD activity which will give you a false negative result.
Remember, G6PD creates NADPH, which is important antioxidant.
Sickle cell anemia is inherited in what manner?
What is the mutation?
Autosomal recessive
Problem in beta globin chain (so chromosome 11). Mutation is at position 6 and results in glutamic acid being replaced with valine (hydrophobic).
Think: sickle - six - glutamic (rhymes sort of)
Describe the chromosomes and # of genes with alpha and beta globin chains.
Alpha globin chain is on chromosome 16 and has 4 genes (2 on each chromosome).
Beta globin chain is on chromosome 11 and has 2 genes (1 on each chromosome).
Only way I have come up with remembering this is:
alpha: think 4 x 4 = 16 (4 genes on C16)
Beta: think 1+ 1 = 2 (C11 and 2 genes)
Describe the thalassemias (alpha and beta).
Alpha:
- Loss of one = silent carrier
- Loss of 2 = mild anemia or may be asymptomatic
- Loss of 3 = HbH disease. Moderate anemia.
- Infant will have inc % of HbBarts (4 gamma chains) up to 20-30%
- Child will have inc % of HbH (4 beta chains) up to 4-20%
- Loss of 4 = HbBarts disease. Think Barts is BAD
- No alpha chains so cant make HbF or HbA. Rare. Very severe. Hydrops.
Beta:
- Loss of one = thalassemia trait. Mild increase in HbA2, HbF
- Loss of 2 = thalassemia disease
- Tricky because can have B zero which makes no beta chains or B plus which makes some beta chains.
- Beta zero: severe anemia, splenomegaly, requires chronic transfusions. Will have > 90% HbF and inc HbA2 (2a, 2d)
- Beta plus: moderate anemia, may not require transfusions. Will have Some HbA but increase in HbF
Coagulation cascade:
- List the components in the extrinsic pathway, intrinsic pathway, common pathway.
- Which has PT? Which has PTT?
Extrinsic: 7, 3
Intrinsic: 12, 11, 9, 8.
Common: 10, 5, 2, 1 (these are dollar $$ numbers)
PT = extrinsic. Think: Play Tennis outside = PT extrinsic pathway
PTT = intrinsic. Think: Play Table Tennis inside = PTT intrinsic pathway
List the change in coags that occur with the following:
Hemophilia A
Hemophilia B
Hemophilia C
F13 deficiency
Von willebrand disease
Vit K deficient bleeding
-Hemophilia A = issue with F8 = very prolonged PTT
-Hemophilia B = issue with F9 = very prolonged PTT
-Hemophilia C = issue with F11 = prolonged PTT
-Factor 13 deficiency: everything will be normal! Will look like a hemophilia but then coags are WNL. F13 responsible for stabilizing fibrin clot
-Von willebrand disease = problem with vWF -> issue with platelet adhesion and issue with F8 ==> delayed bleeding time (normal plt number) and normal to inc PTT
-Vit K deficient bleeding = prolonged PT at first. If goes on longer, then will get prolonged PTT as well.
Describe the KB test and the apt test.
Kleinhauer-Betke test: Blood from MOM. Exposed to acid, which denatures adult Hb making ghost cells. Fetal Hb is resistant to denaturation by the acid so it will remain red. Count # of fetal cells and maternal cells.
- Calculation: (# fetal cells / # maternal cells) x 100
- Every 1% ==> 50ml of fetal blood
Apt test: sample taken from BABY, like bloody gastric sample or stool. Exposed to NaOH (alkali) - which will denature adult Hb. If it is fetal Hb then will be pink. If adult Hb then will be yellow brown.
Both tests rely on fetal Hb being resistant to changes and remaining red/pink.
Diamond Blackman anemia vs Fanconi anemia: similarities and differences
Both have macrocytic anemia with low retic and abnormal thumbs.
But Fanconi also has low WBC and plt and abnormal radius bilaterally.
DBA = pure red cell aplasia —> macrocytic anemia with low retic.
- Inc serum EPO, normal to inc WBC and plt.
- Congenital anomalies in 40%
- Triphalgeal thumbs!!
- Cardiac, renal abnormalities. Low BW, short stature
Fanconi = total marrow hypoplasia —> macrocytic anemia with low retic, low WBC and plt.
- Abnormal thumbs AND abnormal ulna/radius
- Cafe-au-lait spots
For my own confused mind:
- Schwachman-Diamond syndrome: pancytopenia with PANCREATIC INSUFFICIENCY and skeletal abnormalities
-TAR: Severe thrombocytopenia with absent/reduced megakarocytes, bilateral absent radii and ulnar abnormalities with NORMAL THUMBS/DIGITS, 30% with cardiac (TOF)
Inheritance of the following;
Hemophilia A
Hemophilia B
Hemophilia C
F13 deficiency
DBA
Fanconi anemia
TAR
Sickle cell
G6PD
Pyruvate kinase deficiency
Hemophilia A - XLR
Hemophilia B - XLR
Hemophilia C - AR
F13 deficiency - AR
DBA - AD or AR
Fanconi anemia - AR
TAR - AR
Sickle cell - AR
G6PD - XLR
Pyruvate kinase deficiency - AR
Which of the following is not associated with Wilms tumor?
Beckwith-Wiedemann Syndrome
Denys-Drash Syndrome
Pearlman Syndrome
WAGR Syndrome
Wiscott-Aldrich Syndrome
Wiscott-Aldrich is NOT associated with wilms tumor. It is immune deficiency, thrombocytopenia and eczema. They do have increased risk of malignancies such as leukemia and B cell lymphoma.
-You know BW and WAGR (wilms, aniridia, GU anon, mental retardation)
-Denys Dash San: progressive renal disease (nephropathy), wilms tumor, and ambiguous/Female genitalia in males. (Think kidneys and GU)
-Pearlman Syndrome: Germline mut -> overgrowth w/ fetal gigantism, visceromegaly, renal harmatomas and wilms tumor. So overgrowth like BW- has association with wilms.
